Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK-3-ß activation to enhance protein degradation and attenuate nuclear translocation of ß-catenin.

The aim of our study was to investigate the mechanisms by which rhubarb regulates ß-catenin as well as metastasis of hepatocellular carcinomas. Our results revealed that rhubarb extract inhibited HA22T cell migration ability in wound healing, migration and invasion assays in a dose-dependent manner. Rhubarb also reduced ß-catenin protein level, downregulated its downstream proteins, cyclin D, Tbx3 and c-Myc, and attenuated the expression of MMP9 and contactin-1 metastatic factors. Additionally, rhubarb inhibited ß-catenin nuclear accumulation and induced its degradation via proteasome-mediated pathway. Furthermore, we found that rhubarb suppressed the p-ser(9) GSK-3-ß protein level to inactivate Wnt signalling and reduce ß-catenin protein level. Taken together; we found that rhubarb blocked the metastatic process of HA22T hepatocellular carcinoma cells mediated through GSK-3-ß activation, and enhancement of protein degradation as well as reduction of the nuclear accumulation of ß-catenin.